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BIG PHYSICS, BIG QUESTIONS –

Painful memories eased by inhaling xenon gas

By Michael Slezak

It’s odourless, colourless, tasteless and mostly non-reactive – but it may help you forget. Xenon gas has been shown to erase fearful memories in mice, raising the possibility that it could be used to treat post-traumatic stress disorder (PTSD) if the results are replicated in a human trial next year.

The method exploits a neurological process known as “reconsolidation”. When memories are recalled, they seem to get re-encoded, almost like a new memory. When this process is taking place, the memories become malleable and can be subtly altered.

This new research suggests that at least in mice, the reconsolidation process might be partially blocked by xenon, essentially erasing fearful memories. Among other things, xenon is used as an anaesthetic.

Frozen in fear

Edward Meloni and his colleagues at Harvard Medical School in Boston trained mice to be afraid of a sound by placing them in a cage and giving them an electric shock after the sound was played. Thereafter, if the mice heard the noise, they would become frightened and freeze.

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Later, the team played the sound and then gave the mice either a low dose of xenon gas for an hour or just exposed them to normal air. Mice that were exposed to xenon froze for less time in response to the sound than the other mice.

When mice that weren’t exposed to xenon were later placed in the cage where the sound and shocks were produced, they spent 70 per cent of the first two minutes frozen. But mice that had been given xenon treatment spent less than 30 per cent of the time frozen. Playing the sound cue induced more fear in the xenon-exposed mice, but they still only spent about 40 per cent of the two minutes following the sound frozen. “It was as though the animals no longer remembered to be afraid of those cues,” says Meloni.

Forget and fear not

“Unlike other drugs or medications that may also block NMDA receptors involved in memory, xenon gets in and out of the brain very quickly,” says Meloni. “This suggests that xenon could be given at the exact time the memory is reactivated, and for a limited amount of time, which may be key features for any potential therapy used in humans.”

“This is an interesting study, which opens lots of questions for future research,” says Elizabeth Phelps of New York University, who studies the interplay between memory and fear. But she warns that such work has limitations. “These are simple associative threat memories. Many people use these paradigms to study aversive memory representations that are relevant to understanding PTSD, but the evidence that this simple learning model is a sufficient model for the extensive pathology that encompasses PTSD is not great.”

Nevertheless, Meloni says it’s a useful guide, and helps us to understand the dysfunctional learning and memory process involved in maintaining some aspects of PTSD. He hopes to start trials on healthy humans within a year, and if that works, move on to patients who have been diagnosed with PTSD.